Autonomous nanorobots represent an advanced tool for precision therapy to improve therapeutic efficacy. However, current nanorobotic designs primarily rely on inorganic materials with compromised biocompatibility and limited biological functions. Here, we introduce enzyme-powered bacterial outer membrane vesicle (OMV) nanorobots. The immobilized urease on the OMV membrane catalyzes the decomposition of bioavailable urea, generating effective propulsion for nanorobots. This OMV nanorobot preserves the unique features of OMVs, including intrinsic biocompatibility, immunogenicity, versatile surface bioengineering for desired biofunctionalities, capability of cargo loading and protection. We present OMV-based nanorobots designed for effective tumor therapy by leveraging the membrane properties of OMVs. These involve surface bioengineering of robotic body with cell-penetrating peptide for tumor targeting and penetration, which is further enhanced by active propulsion of nanorobots. Additionally, OMV nanorobots can effectively safeguard the loaded gene silencing tool, small interfering RNA (siRNA), from enzymatic degradation. Through systematic in vitro and in vivo studies using a rodent model, we demonstrate that these OMV nanorobots substantially enhanced siRNA delivery and immune stimulation, resulting in the utmost effectiveness in tumor suppression when juxtaposed with static groups, particularly evident in the orthotopic bladder tumor model. This OMV nanorobot opens an inspiring avenue to design advanced medical robots with expanded versatility and adaptability, broadening their operation scope in practical biomedical domains.

中文翻译：

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细菌外膜囊泡纳米机器人


自主纳米机器人代表了精确治疗以提高治疗效果的先进工具。然而，当前的纳米机器人设计主要依赖于生物相容性较差且生物功能有限的无机材料。在这里，我们介绍酶驱动的细菌外膜囊泡（OMV）纳米机器人。 OMV膜上固定的脲酶催化生物可利用尿素的分解，为纳米机器人产生有效的推进力。这种 OMV 纳米机器人保留了 OMV 的独特功能，包括内在的生物相容性、免疫原性、实现所需生物功能的多功能表面生物工程、货物装载和保护能力。我们提出了基于 OMV 的纳米机器人，旨在利用 OMV 的膜特性进行有效的肿瘤治疗。这些涉及机器人身体的表面生物工程，具有用于肿瘤靶向和渗透的细胞穿透肽，这通过纳米机器人的主动推进进一步增强。此外，OMV纳米机器人可以有效保护加载的基因沉默工具小干扰RNA（siRNA）免遭酶促降解。通过使用啮齿动物模型的系统性体外和体内研究，我们证明这些 OMV 纳米机器人显着增强了 siRNA 递送和免疫刺激，与静态组并置时可实现最大的肿瘤抑制效果，在原位膀胱肿瘤模型中尤其明显。这款 OMV 纳米机器人为设计具有扩展多功能性和适应性的先进医疗机器人开辟了一条鼓舞人心的途径，拓宽了其在实际生物医学领域的操作范围。